Liposomes containing active agents

Abstract

Liposomes formulations are designed to maximize the amount of poorly water-soluble active agent that can be carried by the liposome. Liposomes containing active agent in the lipid bilayer of the liposome, and/or entrapped within the liposome interior space in a micellar preparation are described. Methods of making such liposomes are presented.

That which is claimed is: 
     
       1. A liposome containing an active agent, said liposome comprising: (a) a lipid unilaminar bilayer comprising phospholipid, lipid surfactant with a Critical Micelle Concentration (CMC) of about 1 millimolar or less, and from 3 mole percent to 60 mole percent of cholesterol; and   (b) a micellar preparation comprising active agent aggregated with the lipid surfactant to form micelles, said micelles entrapped within the interior space of the liposome; and said cholesterol is contained in the lipid bilayer in an amount sufficient to increase the stability of the micelle-containing liposome compared to that which would occur in the absence of cholesterol.     
     
     
       2. A liposome according to claim 1, wherein said lipid bilayer further comprises active agent associated with the lipid bilayer. 
     
     
       3. A liposome according to claim 1, wherein said phospholipid is stearoyloleoylphosphatidylcholine (SOPC). 
     
     
       4. A liposome according to claim 1, wherein said surfactant is a lysolipid. 
     
     
       5. A liposome according to claim 1, wherein said surfactant is a lysophosphatidylcholine. 
     
     
       6. A liposome according to claim 1, wherein said surfactant is monooleyolphosphatidylcholine (MOPC). 
     
     
       7. A liposome according to claim 1, wherein said active agent is paclitaxel. 
     
     
       8. A liposome according to claim 7, wherein paclitaxel is contained in the liposome in an amount of at least 7 mol % relative to SOPC. 
     
     
       9. A liposome according to claim 1, said lipid bilayer further comprising polymer-derivatized lipids. 
     
     
       10. A liposome according to claim 9, wherein said polymer is polyethylene glycol. 
     
     
       11. A liposome according to claim 1, wherein said lipid bilayer comprises phospholipid, cholesterol and surfactant in a mole ratio of about 8:4:3. 
     
     
       12. A liposome containing paclitaxel, said liposome comprising: (a) a lipid unilaminar bilayer comprising phospholipid, lysophosphatidylcholine, and cholesterol in a mole ratio of about 8:4:3, and   (b) a micellar preparation comprising paclitaxel aggregated with lysophosphatidylcholine micelles, said micelles entrapped within the interior space of the liposome.   
     
     
       13. A liposome according to claim 12, further comprising paclitaxel associated with the lipid bilayer. 
     
     
       14. A liposome according to claim 13, wherein said phospholipid is SOPC and wherein paclitaxel is contained in the liposome in an amount of at least 7 mol % relative to SOPC.